Treatment of men with localized prostate cancer at diagnosis usually consists of potentially curative radical prostatectomy or radiation therapy (1).
However, a significant percent of these men progress to a condition known as advanced prostate cancer. Such “advanced” cancer requires additional therapy beyond surgery and/or radiation and many men develop metastatic disease. The treatment of choice for this condition is androgen ablation therapy which has been found to be palliative, not curative, although it can slightly improve the likelihood of survival. The majority of patients with advanced disease eventually progress to an androgen-independent stage (AID), also known as hormonal refractory prostate cancer (HRPC), which is unresponsive to further hormonal therapy, does not result in long-term survival, and whose best outcome is to maintain or to improve their quality of life.
Therapeutic options for patients with AID prostate cancer are limited, with lack of evidence for long-term survival. The current treatment for AID patients is chemotherapy with such agents as Docetaxel, Paclitaxel, Estramustine, Mitoxantrone, Vinorelbine and Doxorubicin, given alone or in combination. In some patients, clinically-effective chemotherapy may initially cause regression of a cancer, but the cancer invariably recurs due to cancer cells that recover, proliferate, and often metastasizes.
The chemotherapy standard of care, despite only minimal benefits, is Docetaxel. It provides only marginal improvements in survival for such patients (2, 3).
For any antitumor agent to be effective in AID refractory prostate cancer, it must arrest the proliferation of the cancer cells and/or also cause their death either by necrosis (i.e., cytotoxic anticancer agents/chemotherapy) or apoptosis (i.e., non-cytotoxic anticancer agents).
There is no pharmaceutical currently available, whether cytotoxic or non-cytotoxic, that can be considered as an effective treatment for this aggressive cancer. The median response to hormonal ablative therapy in patients with known metastatic disease has been reported to vary between 18 months and 3 years (4).